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Infective endocarditis (IE) is a serious infection and causes significant morbidity and mortality. However, the benefit of surgery for endocarditis besides antibiotic treatment in dialysis patients remains controversial. We performed a systematic review of studies published between 1960 and February 2022. Meta-analysis was conducted with a random-effects model to explore the in-hospital, 30, 60, 90, 180-d, and 1-year mortality rates in adult dialysis patients with IE. Sensitivity analysis, subgroup analysis, and meta-regression were performed to explore potential sources of heterogeneity. Confidence of evidence was evaluated by the GRADE system. Thirteen studies were included. The pooled odds ratio of in-hospital mortality was 0.62 (95% confidence interval [CI]: 0.30–1.28, p =.17), with moderate heterogeneity (I2 = 62%, p <.01). Three studies reported 30-d mortality, and the pooled odds ratio for surgery compared with medical treatment was even lower (0.36; 95% CI: 0.22–0.61, p <.01), with low heterogeneity (I2 = 0%, p =.86). With studies on fewer than 30 patients excluded, the sensitivity analysis revealed a low odds ratio of in-hospital mortality for surgery versus medical treatment (0.52; 95% CI: 0.27–0.99, p =.047), with moderate heterogeneity (I2 = 63%, p <.01). Subgroup analysis revealed no significant differences between any two comparator subgroups. Based on a very low strength of evidence, compared with medical treatment, surgical treatment for IE in patients on dialysis is not associated with lower in-hospital mortality. When studies on fewer than 30 patients were excluded, surgical treatment was associated with better survival. [ABSTRACT FROM AUTHOR]

Uncoupling of mitochondrial respiration by chemical uncouplers has proven effective in ameliorating obesity, insulin resistance, and hyperglycemia. However, development of uncoupler-based therapy remains challenging due to its potentially lethal adverse effects. Here, we identify pyruvate dehydrogenase (PDH) as a key modifier of the toxicity profile of 2, 4-dinitrophenol (DNP), a prototypical mitochondrial uncoupler. PDH activation by dichloroacetic acid (DCA) protects mice from DNP-induced hyperlactacidemia, hyperthermia, and death while preserving the ability of DNP to promote fuel oxidation and improve insulin sensitivity in mice. Mechanistically, PDH activation switches on mitochondrial glucose oxidation to accommodate increased glycolytic flux, leading to reduced lactate secretion during uncoupler treatments. We devised a chemical screening strategy and discovered compound 6j as a dual-action compound that simultaneously activates PDH and uncouples mitochondrial respiration. Compound 6j exhibits an excellent efficacy and safety profile in restoring glucose homeostasis in diabetic mice. This work establishes a new principle to safely harness the power of chemical uncouplers for the treatment of metabolic disease. [ABSTRACT FROM AUTHOR]

Clove oil exhibits antimicrobial activities against a wide range of pathogenic microorganisms. Microencapsulation technology can be used to improve its stability and water solubility. The actual application of clove oil microcapsule on the antifungal preservation of meat products, such as cooked fish, cooked chicken, cooked pork, and cooked beef, was investigated in this study. Results showed that clove oil microcapsule displayed good antiseptic effects on these meat products at an effective fungicidal concentration of above 0.070%. Even if the meat was boiled for 0.5 h, the efficiency of clove oil microcapsule increased to 0.080%. Clove oil microcapsules had a trong heat resistance and high inhibition effect on meat products, and their disease indices and variation rates of mold spores also decreased. As a novel alternative, clove oil microcapsule had practical applications as a preservative in meat products, especially in foods requiring heat processing. [ABSTRACT FROM AUTHOR]

Objective We aimed to compare the kinetics of white blood cell (WBC) and explore predictive factors of leukocytosis in non-high-risk acute promyelocytic leukemia (APL), with oral arsenic plus all-trans retinoic acid (ATRA) or intravenous arsenic trioxide (ATO) plus ATRA as a first-line treatment. Methods The absolute count, doubling time and peak time of WBC were analyzed in 64 newly diagnosed non-high-risk APL patients who were treated with different induction regimens containing either oral Realgar-indigo naturalis formula (RIF) (n = 35) or ATO (n = 29). The end points were the dynamic changes of the WBC counts during induction. The time points started at day 1 and were selected over 3-day intervals for 28 days. Results Among the 64 included patients, the median initial and peak WBC counts were 1.78 × 10 9 /L (range 0.31–9.89) and 12.16 × 10 9 /L (range 1.56–80.01), respectively. The incidence of differentiation syndrome was 9.38%. The dynamic changes in leukocytosis showed a single peak wave in all the patients, and the median time to peak was 10 (range 2–26) days. A higher WBC count was observed in the RIF group than in the ATO group after 10 days of treatment (9.22 × 10 9 /L vs. 4.10 × 10 9 /L, p = 0.015). Patients with the peak WBC count > 10 × 10 9 /L had a shorter WBC doubling time compared to patients with a lower peak WBC (RIF group 4 days vs. 7 days, p = 0.001; ATO group 4.5 days vs. 23 days, p = 0.002). Univariate and multivariable analyses showed that the doubling time of WBC is an independent factor for the peak WBC count. Conclusion Different kinetics of WBC proliferation were observed during induction with oral arsenic plus ATRA and ATO plus ATRA. The doubling time of WBC is an important independent factor for predicting the peak WBC count. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate whether 1 mA of percutaneous electrical stimulation (ES) at 0, 2, 20, or 200 Hz augments regeneration between the proximal and distal nerve stumps in streptozotocin diabetic rats. A10-mm gap was made in the diabetic rat sciatic nerve by suturing the stumps into silicone rubber tubes. Normal animals were used as the controls. Starting 1 week after transection, ES was applied between the cathode placed at the distal stump and the anode at the proximal stump every other day for 3 weeks. At 4 weeks after surgery, the normal controls and the groups receiving ES at 20, and 200 Hz had a higher success percentage of regeneration compared to the ES groups at 0 and 2 Hz. In addition, quantitative histology of the successfully regenerated nerves revealed that the groups receiving ES at a higher frequency, especially at 200 Hz, had a more mature structure with more myelinated fibers compared to those in the lower-frequency ES groups. Similarly, electrophysiology in the ES group at 200 Hz showed significantly shorter latency, larger amplitude, larger area of evoked muscle action potentials and faster conduction velocity compared to other groups. Immunohistochemical staining showed that ES at a higher frequency could significantly promote calcitonin gene-related peptide expression in lamina I-II regions in the dorsal horn and recruit a higher number of macrophages in the diabetic distal sciatic nerve. The macrophages were found that they could stimulate the secretion of nerve growth factor, platelet-derived growth factor, and transforming growth factor-β in dissected sciatic nerve segments. The ES at a higher frequency could also increase cutaneous blood flow in the ipsilateral hindpaw to the injury. These results indicated that a high-frequency ES could be necessary to heal severed diabetic peripheral nerve with a long gap to be repaired. [ABSTRACT FROM AUTHOR]

The aim of our study was to evaluate the impact of oral arsenic (the realgar-indigo naturalis formula, RIF) and all-trans retinoic acid (ATRA) on coagulopathy in acute promyelocytic leukemia (APL) compared with intravenous arsenic trioxide (ATO) and ATRA during induction. Mitoxantrone was added to all the patients at a dose of 1.4 mg/m 2 per day for 5–7 days. D-dimer levels, prothrombin time (PT), fibrinogen (Fbg) levels and the platelet count were comparably analyzed among 83 newly diagnosed APL patients treated with RIF (n = 45) or with ATO (n = 38). Since induction therapy with RIF and ATRA, the median levels of Fbg, PT and platelets were recovered to the normal range within 4 days, 10 days and 28 days, respectively. The last day of platelet and plasma transfusion was day 12 (range: 0–24 days) and day 3 (range: 0–27 days), respectively. Among the 42 patients with a disseminated intravascular coagulation (DIC) score = 4, the consumption of transfused platelets was less in the RIF group than that in the ATO group ( P = 0.037). In the 17 patients with a DIC score <4, prompt recovery of Fbg levels ( P = 0.028) was observed in the RIF group compared with that in the ATO group ( P = 0.401). RIF and ATO showed similar effects on the recovery of coagulopathy in APL patients. RIF had a potential beneficial effect in accelerating the recovery of thrombocytopenia and hypofibrinogenemia for subclinical DIC patients. [ABSTRACT FROM AUTHOR]

Radix Bupleuri (RB), with a Chinese name Chaihu, is one of the most popular Traditional Chinese herbal drug. It can be baked with vinegar to afford vinegar-baked Radix Bupleuri (VBRB), which is used in Traditional Chinese Medicine (TCM) for liver diseases treatment. In the present study, nuclear magnetic resonance-based metabolomic approach was used to compare the liver protective effect of RB and two types of VBRBs, which were prepared by two kinds of vinegar. The contents of 14 metabolites in the liver of carbon tetrachloride (CCl 4 ) treated mice were significantly altered in comparison with control group, and VBRB prepared by Shanxi vinegar showed best effect as revealed by the amount and regulatory degree of the perturbed metabolites. The metabolism pathways analysis showed that the liver protective effect was related with the energy metabolism, lipid metabolism, ketone body metabolism, glutathione metabolism, amino acids metabolism and nucleotide synthesis. The results presented here showed that metabolomic approach made it possible to disclose the subtle biological difference between two types of VBRB, which highlight the potential of metabolomic approach to quantitatively compare the pharmacological effect of the herbal drugs. [ABSTRACT FROM AUTHOR]

Background: Pritelivir is a novel helicase-primase inhibitor in clinical development for treatment of herpes simplex virus type 2 (HSV-2) infections. In preclinical work, resistance-mediating mutations were identified in the HSV-2 genome at 3 loci in the UL5 gene and 1 locus in UL52.Methods: To evaluate whether daily pritelivir treatment results in emergence of resistance-mediating mutations, we analyzed HSV-2 strains detected in genital swab specimens from trial participants who were randomly assigned to receive different dosages of pritelivir. We sequenced resistance regions from 87 participants' samples, the UL5 gene in 73 samples from 44 participants, and the UL52 gene in 71 samples from 43 participants.Results: We found no evidence that pritelivir induced known resistance-mediating mutations or for amino acid variation at other loci. In one participant's HSV-2 isolate, we found a previously unidentified mutation close to the putative resistance-mediating region in UL5 and subsequently determined in vitro susceptibility to pritelivir. We characterized mutations from 32 cultivated HSV-2 isolates previously found to be susceptible to pritelivir in vitro and identified several novel mutations that most likely reflect preexisting variation in circulating HSV-2.Conclusions: This study demonstrates evidence of retained susceptibility of HSV-2 to pritelivir in immunocompetent persons following daily therapy for up to 28 days. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis compared survival and function in patients with limb osteosarcoma treated with limb-salvage surgery (LSS) versus amputation or rotationplasty. Methods: Medline, Cochrane, EMBASE, and Google Scholar were searched until November 30, 2015 for studies reporting Musculoskeletal Tumor Society (MSTS) scores and survival rates in osteosarcoma patients. Differences between patients undergoing LSS versus ablative surgery were analyzed based on MSTS scores and postoperative survival rates. Results: Of 1330 patients in the studies analyzed, 934 underwent LSS, and 662 were treated with amputation. A random-effects model was applied due to heterogeneity among studies ( Q statistic = 1.829, I = 0 %, p = 0.767). No difference was found in post-operative local recurrence rate between amputees and patients receiving LSS. The 5-year survival rate was significantly lower with amputation compared with LSS (OR 0.628; 95 % CI 0.431-0.913, p = 0.015). The 2-year survival rate was not different between amputation and LSS. In addition, amputees had lower MSTS scores than those undergoing LSS (difference in means = −4.46 %, 95 % CI 6.49-2.45 %, p < 0.001). Conclusions: LSS results in higher 5-year survival rates and better functional outcomes as indicated by MSTS scores in patients with limb osteosarcomas. [ABSTRACT FROM AUTHOR]

To prepare ethosomes containing tea tree oil by hot homogenization method and to evaluate its physical characters and in vitro release pattern. The preformulation studies were carried out by standard procedure. The morphology of globule was studied by optical microscopy. The globule size and zeta potential was determined by Zetasizer, respectively and in vitro study was done by diffusion method and the drug content was analyzed by HPTLC method. The release kinetics was also studied by fitting into few mathematical models. All the formulations were showed spherical and unilamellar shape with globule size of 931 to 975nm, the zeta potential in the range of - 40 to -52mV and entrapment efficiency was 57 to 65%. Finally the in vitro release studies showed the drug release from the ethosomal vesicles was burst release at initial time followed by sustained release over throughout the study. From the above consideration of evaluation studies, the tea tree oil loaded ethosomal formulation F5 shows best globule size, zeta potential and entrapment efficiency. The sustained action was confirmed by in vitro release studies. All the formulations are followed zero order drug release and diffusion type of mechanism of drug releases with Fickian model. Ethosome loaded tea tree oil could be the best choice for topical application. [ABSTRACT FROM AUTHOR]

Purpose: To study if electrical stimulation (ES) can be a useful tool to improve functional recovery after neuronal injury in the peripheral nervous system. Methods: We studied the effects of 2 Hz of percutaneous ES at different intensities of 1, 10 and 20 mA on peripheral nerve regeneration in rats with diabetes induced by streptozotocin. Non-stimulated diabetic rats were used as the sham-controls. A10-mm gap was made in the rat sciatic nerve by suturing the stumps into silicone rubber tubes and stimulation was carried out every other day for 3 weeks starting 1 week after surgery. Results: After 4 weeks of recovery, the diabetic rats showed that ES of 1 mA or above could increase the cutaneous blood flow in their ipsilateral hindpaw to the injury. ES of 10 mA could improve the amplitude and the area of evoked muscle action potentials with faster target muscle reinnervation. ES of 10 mA could also ameliorate the calcitonin gene-related peptide expression in lamina I-II regions in the dorsal horn ipsilateral to the injury and the number of macrophages in the diabetic distal sciatic nerve. The impaired growth and maturation of regenerating axons in diabetic rat could be improved by ES of 10 mA or above. Conclusions: All these results lead to the conclusion that ES of 10 mA or above might be necessary to improve regeneration after a dissect lesion of the sciatic nerve in the diabetic rat. [ABSTRACT FROM AUTHOR]

Panax notoginseng, a traditional Chinese medicine, has been used for thousands of years to treat ischemic patients. More than 20 saponin components have been isolated from P. notoginseng root and identified chemically. However, these different chemical components have different roles. In this study we compared the neuroprotective mechanisms of ginsenosides Rg1, Rb1, Rg1/Rb1, and panax notoginsenoside (PNS) against injuries caused by cerebral ischemia-reperfusion (I/R). Our results show that all of these treatments significantly reduced infarction volume and alleviated neurological deficits caused by cerebral I/R. The increase in malondialdehyde (MDA) concentration was inhibited by these treatments in the hippocampus. The decreased expressions of thioredoxin-1 (Trx-1), copper-zinc superoxide dismutase (SOD-1), protein kinase B (PKB/Akt), and nuclear factor-kappa B (NF-κB) caused by cerebral I/R were restored by these treatments. The expression of heat shock protein 70 (HSP70) was enhanced in the middle cerebral artery occlusion (MCAO) group, as well as in all of the treatment groups. These results suggest that Rg1 and Rb1 have similar roles in protecting the brain from ischemic damage; however, neither Rg1/Rb1 nor PNS have synergistic effects, thus either Rg1 or the Rb1 monomer should be considered as a pharmacological neuroprotective strategy for use in the case of ischemic stroke. [ABSTRACT FROM AUTHOR]

Abstract: Angiogenesis is closely related to tumor development and metastasis. Osteosarcoma is an angiogenesis-dependent tumor, and studies have shown that chemotherapy often induces angiogenesis. Endostatin is a broad spectrum angiogenesis inhibitor and, while pre-clinical trials have shown that the combination of endostatin with chemotherapy can enhance anti-tumor effects, this effect has not yet been shown in clinical trials. Here, we aimed to evaluate the clinical efficacy of endostar (ES, human recombinant endostatin) combined with chemotherapy in the treatment of osteosarcoma patients. A total of 116 newly diagnosed patients with osteosarcoma were enrolled in this study. All patients received 4cycles of chemotherapy with (54 cases) or without (62 cases) ES. ES was administered intravenously at a dose of 15mg/day for 2weeks during each cycle of chemotherapy. The tumors were removed by surgery after 2cycles of chemotherapy treatment, and their histologic response to chemotherapy was evaluated. Immunohistochemistry was used to measure VEGF and CD 31 expression. Chemotherapy increased VEGF expression and the presence of microvessels in osteosarcoma tissues compared with pre-chemotherapy. No significant difference was observed in the histologic response between the ES treatment and non-treatment groups. However, ES treatment significantly inhibited the chemotherapy-induced VEGF expression and presence of microvessels. The ES treatment did not affect the overall survival rate but did increase the event-free survival rate and decreased the occurrence of metastases. In conclusion, our results indicate that antiangiogenic therapy using ES has the potential to prevent the progression of metastases. [Copyright &y& Elsevier]